Department of Biochemistry, Biology and Genetics, Polytechnic University of the Marche, Ancona, Italy.
Biofactors. 2011 Sep-Oct;37(5):386-92. doi: 10.1002/biof.184.
Structural changes and abnormal function of mitochondria have been documented in Down's syndrome (DS) cells, patients, and animal models. DS cells in culture exhibit a wide array of functional mitochondrial abnormalities including reduced mitochondrial membrane potential, reduced ATP production, and decreased oxido-reductase activity. New research has also brought to central stage the prominent role of oxidative stress in this condition. This review focuses on recent advances in the field with a particular emphasis on novel translational approaches involving the utilization of coenzyme Q(10) (CoQ(10) ) to treat a variety of clinical phenotypes associated with DS that are linked to increased oxidative stress and energy deficits. CoQ(10) has already provided promising results in several different conditions associated with altered energy metabolism and oxidative stress in the CNS. Two studies conducted in Ancona investigated the effect of CoQ(10) treatment on DNA damage in DS patients. Although the effect of CoQ(10) was evidenced only at single cell level, the treatment affected the distribution of cells according to their content in oxidized bases. In fact, it produced a strong negative correlation linking cellular CoQ(10) content and the amount of oxidized purines. Results suggest that the effect of CoQ(10) treatment in DS not only reflects antioxidant efficacy, but likely modulates DNA repair mechanisms.
在唐氏综合征（DS）细胞、患者和动物模型中，已经记录到线粒体的结构变化和功能异常。培养中的 DS 细胞表现出广泛的线粒体功能异常，包括线粒体膜电位降低、ATP 产生减少和氧化还原酶活性降低。新的研究还将氧化应激在这种情况下的突出作用推向了中心舞台。这篇综述重点介绍了该领域的最新进展，特别强调了涉及使用辅酶 Q10（CoQ10）治疗与氧化应激和能量不足增加相关的各种与 DS 相关的临床表型的新转化方法。CoQ10 已经在与中枢神经系统能量代谢和氧化应激改变相关的几种不同情况下提供了有希望的结果。在安科纳进行的两项研究调查了 CoQ10 治疗对 DS 患者 DNA 损伤的影响。尽管 CoQ10 的作用仅在单细胞水平上得到证实，但该治疗会根据细胞中氧化碱基的含量来影响细胞的分布。事实上，它产生了一个强烈的负相关，将细胞内 CoQ10 的含量与氧化嘌呤的量联系起来。结果表明，CoQ10 治疗在 DS 中的作用不仅反映了抗氧化功效，而且可能调节 DNA 修复机制。
